Research Progress on the Combination of PARP Inhibitors (PARPi) and Immune Checkpoint Inhibitors (ICIs)

Abstract

Deficiencies in DNA damage repair (DDR), such as poly (ADP-ribose) polymerase (PARP) deficient, cause cancer development by promoting DNA mutations while also exposing the specificity and vulnerability of cancer to afford a treatment option. PARP inhibitor (PARPi) has shown great prospects in the treatment of tumors carrying homologous recombination (HR) deficiencies, such as germline BRCA1/2 mutations. PARPi leads to an increase in the expression of tumor neoantigen, interferon (IFN), and programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1), which also regulate the tumor microenvironment (TME), promoting a deeper anti-tumor immunotherapy. ICIs targeting PD-1/PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved impressive success in the treatment of malignancies. Considering PARPi do enhance the anti-tumor response of ICIs, the combination of PARPi and ICIs has gradually become an alternative treatment option for individuals not receiving apparent efficacy from ICI monotherapy. In this review, the emphasis will be on the mechanisms and immune responses associated with PARPi, profess the principle, then count the clinical studies of this combination therapy.